LFLG AS Research Articles

Characterisation of coronary microvascular dysfunction in patients with severe aortic stenosis undergoing TAVI.

Microvascular resistance reserve (MRR) is a validated measure of coronary microvascular function independent of epicardial resistances. We sought to assess whether MRR is associated with adverse cardiac remodelling, a low-flow phenotype and extravalvular cardiac damage (EVCD) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Invasive thermodilution-based assessment of the coronary microvascular function of the left anterior descending artery was performed in a prospective, multicentre cohort of patients undergoing TAVI. Coronary microvascular dysfunction (CMD) was defined as the lowest MRR tertile of the study cohort. Haemodynamic measurements were performed at baseline and then repeated immediately after TAVI. EVCD and markers of a low-flow phenotype were assessed with echocardiography. A total of 134 patients were included in this study. Patients with low MRR were more frequently females, had a lower estimated glomerular filtration rate and a higher rate of atrial fibrillation. MRR was significantly lower in patients with advanced EVCD (median 1.80 [1.26-3.30] vs 2.50 [1.87-3.41]; p=0.038) and in low-flow, low-gradient AS (LF LG-AS) (median 1.85 [1.20-3.04] vs 2.50 [1.87-3.40]; p=0.008). Overall, coronary microvascular function tended to improve after TAVI and, in particular, MRR increased significantly after TAVI in the subgroup with low MRR at baseline. However, MRR was significantly impaired in 38 (28.4%) patients immediately after TAVI. Advanced EVCD (adjusted odds ratio 3.08 [1.22-7.76]; p=0.017) and a low-flow phenotype (adjusted odds ratio 3.36 [1.08-10.47]; p=0.036) were significant predictors of CMD. In this observational, hypothesis-generating study, CMD was associated with extravalvular cardiac damage and a low-flow phenotype in patients with severe AS undergoing TAVI.

The prognostic value of left atrial strain in patients with low-flow, low-gradient aortic stenosis

Abstract Background Left atrial (LA) function is known to be an independent prognostic parameter in patients undergoing transcatheter aortic valve replacement (TAVR). However, the impact of LA function on postinterventional outcomes in patients with severe low-flow, low-gradient aortic stenosis (LFLG AS) is unknown. Objectives We aimed to evaluate postinterventional changes and prognostic value of LA strain in patients with LFLG AS who underwent TAVR. Methods We retrospectively included 88 patients (79.66 ± 6.33, 37.5% female) with symptomatic LFLG AS who underwent TAVR at the Heart Center Bonn. LA global function and strain were comprehensively assessed by the postprocessing left atrial phasic strain analysis – LA reservoir strain, LA conduit strain, and LA contractile strain ­– using a commercially available postprocessing software at baseline and three years after the procedure. The apical four-, two-, and three-chamber views with sufficient image quality were used for strain analysis. Results Baseline LA strain was found to be impaired in all patients (reservoir: 13.17 ± 7.62 %; conduit: 6.7 ± 6.4 %; contractile: -1.7 ±1.5 %). All-cause mortality was 41 % three years after the procedure. In the overall collective, LA reservoir strain was increased at follow-up (13.17 ± 7.62 % to 15.21 ± 10.13 %, p= 0.049), whereas conduit and contractile strain remained unchanged (p > 0.05). According to the survival at follow-up, we divided the cohort into survivors and non-survivors. Baseline reservoir (14.55 ± 8.14 % vs 9.59 ± 5.23 %, p= 0.002) and conduit (7.66 ± 7.14 % vs 4.44 ± 4.1 %, p= 0.017) strain were significantly higher in survivors. All LA strain parameters were significantly improved in survivors at follow-up. In contrast, non-survivors showed no relevant changes in LA strain parameters. In comparison of ROC curves, reservoir strain was found to be the best predictor for postinterventional survival after TAVR (reservoir AUC: 0.677, cutoff: 10 %, p = 0.007; conduit AUC: 0.642, cutoff: 3.7 %, p = 0.037; contractile AUC: 0.672, cutoff: -1,3 %, p = 0.008). Concordantly, we found that all LA strain parameters are independent predictors for three-year all-cause mortality after TAVR in cox regression analysis (reservoir OR: 0.89, p=0.005; conduit OR: 0.90, p=0.03, contractile OR: 0.71, p=0.029) in cox regression analysis. According to multivariate analysis, reservoir strain (OR: 0.91, p=0.05) and conduit strain (OR: 0.94, p=0.04) were found to be independent predictors for postinterventional survival. According to log-rank analysis, patients with a baseline reservoir strain < 10 % and a baseline conduit strain < 4 %) showed significantly higher mortality (p = 0.048). Conclusion Using LA strain parameters might optimize risk stratification and better decision-making with sufficient patient selection in this vulnerable cohort.

The diagnostic role of acceleration time measurement in patients with classical low flow low gradient aortic stenosis with reduced left ventricular ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. Background Low-flow, low-gradient (LF-LG) AS can occur with a reduced or preserved left ventricular ejection fraction (LVEF) and is difficult to diagnose in either case(1). The main challenge is to distinguish between true severe and pseudo-severe stenosis. Dobutamine stress echocardiography (DSE) is recommended for the distinction of stenosis severity and LV flow reserve in classical LF-LG AS(2). Individual dissimilarities can be seen in the DSE results depending on the severity of the AS and LV afterload mismatch and/or on the existence of accompanying cardiomyopathy(3). One-third of the classical LF- LG AS with reduced LVEF patients do not have LV flow reserve (an increase of less than 20% in SV during DSE)(2). This patient group with an indeterminate DSE result has high surgical risk, and additional examinations are always required(4). Purpose The aim of our study was to evaluate the role of Acceleration time (AT), Ejection time (ET), and AT/ET ratio in predicting DSE outcome in classical LF-LG AS patients with reduced EF, and to distinguish between true and pseudo AS to determine the cut-off for AT which can be a useful evalu- ation method in clinical practice. Methods Sixty-seven classical LF-LG AS with reduced LVEF patients who underwent dobutamine stress echocardiography (DSE) were included in the study. Patients with ventricular arrhythmia and pace rhythm, moderate and severe mitral stenosis, severe aortic insufficiency, and paradoxical LF-LG AS patients were excluded. According to DSE results, all patients were divided into two groups; true AS and pseudo-severe AS. Aortic valve calcium score was measured in patients with inconclusive DSE results. AT and other ejection dynamics (ET and AT/ET) were calculated by taking baseline echocardiographic records into account for all patients(1,5). The predictive power of AT and other ejection dynamics were evaluated to estimate true and pseudo-severe AS. Results According to DSE results, out of 67 patients, 44 (65.7%) was diagnosed as true severe AS. There was a statistically significant relation between baseline AT and true AS [adjusted OR 4.47 (95% CI 1.93–10.4), p = 0.001]. The best cutoff value of AT was measured as 100 msec according to the Youden index. This value had a sensitivity value of 77%, specificity value of 87%, positive predictive value of 92%, and a negative predictive value of 67%. Conclusion In conclusion, the biggest difference of our study from the other studies in the literature is that we only included LF-LG AS patients with reduced EF in our study. Additionally, the study assesses the predictive strengths of ejection dynamics, one by one, regarding DSE results, and therefore, assesses role of ejection dynamics role to distinguish true and pseudo severe AS. As a result of our analysis, AT has a diagnos- tic role in the determination of true severe AS. Large-scale studies are needed to be carried out regarding true severe AS among LF LG AS patients with reduced LVEF.

P18 PROGNOSTIC IMPACT OF MITRAL REGURGITATION BEFORE AND AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT IN PATIENTS WITH SEVERE LOW FLOW, LOW GRADIENT AORTIC STENOSIS

Abstract Background There is little evidence about the prognostic role of mitral regurgitation (MR) in patients with low flow, low gradient aortic stenosis (LFLG–AS) undergoing transcatheter aortic valve replacement (TAVR). Aims: The aim of this study was to assess the prevalence and outcome implication of moderately severe to severe MR in patients with LFLG–AS before and after TAVR. Methods This study included consecutive patients with LFLG–AS undergoing TAVR at two Italian high–volume centres. The study population was categorized according to the baseline MR severity and to the presence of MR improvement at discharge. The primary outcome was the composite of all–cause death and hospitalization for worsening heart failure (HF) up to one year. The secondary outcomes were the single components of the primary outcome. Results The study included 268 patients; 57 (21%) patients showed MR>2+. Patients with MR>2+ showed a lower one–year survival free from the primary outcome (Log–Rank <0.001; Figure1), all–cause death (Log–Rank <0.001), and HF hospitalization (Log–Rank <0.001) compared to patients with MR≤2+. At multivariable analysis, baseline MR>2+ was an independent predictor of the primary outcome (p<0.001). Among patients with baseline MR>2+, MR improvement was reported in 24 (44%) cases after TAVR. The one–year survival free from the primary outcome was significantly higher in patients with MR improvement than in those without (Log–Rank = 0.009), and both groups had a significantly lower survival free from the primary outcome when compared with patients with baseline MR <2+ (Figure 2). One–year survival free from the all–cause death (Log–Rank = 0.036) and HF hospitalization (Log–Rank = 0.005) was consistently higher in patients with MR improvement than in those without. Conclusions In this study, the presence of moderately severe to severe MR in LFLG–AS patients undergoing TAVR portend a worse clinical outcome at one year. TAVR may improve MR severity in nearly half of the patients, resulting in a potential outcome benefit after discharge.

Left ventricular reverse remodeling after transcatheter aortic valve implantation in patients with low-flow low-gradient aortic stenosis

ObjectivesLeft ventricular reverse remodeling (LVRR) is associated with improved outcome in patients with heart failure. Factors associated with and predictive of LVRR in patients with low-flow low-gradient aortic stenosis (LFLG AS) after transcatheter aortic valve implantation (TAVI) and its impact on outcome were assessed. MethodsPre- and postprocedural left ventricular (LV) function and volume were investigated in 219 patients with LFLG. LVRR was defined as an absolute increase of ≥10% in LV ejection fraction (LVEF) and reduction of ≥15% in LV end-systolic volume (LVESV). The primary endpoint was the combination of all-cause mortality and rehospitalization for heart failure. ResultsThe mean LVEF was 35.0 ± 10.0%, with a stroke volume index (SVI) of 25.9 ± 6.0 mL/m2 and LVESV of 94.04 ± 46.0 mL. At a median of 5.2 months (interquartile range, 2.7–8.1 months), 77.2% (n = 169) of the patients showed echocardiographic evidence of LVRR. A multivariate model revealed three independent factors for LVRR after TAVI: SVI of <25 mL/m2 (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.08–3.58; p < 0.01), LVEF of <30% (HR, 2.76; 95% CI, 1.53–2.91; p < 0.01), and valvulo-arterial impedance (Zva) of <5 mmHg/mL/m2 (HR, 5.36; 95% CI, 1.80–15.98; p < 0.01). Patients without evidence of LVRR showed a significantly higher incidence of the 1-year combined endpoint (32 [64.0%] vs. 75 [44.4%], p < 0.01). ConclusionsThe majority of patients with LFLG AS show LVRR after TAVI, which is associated with favorable outcomes. An SVI of <25 mL/m2, LVEF of <30%, and Zva < 5mmHg/mL/m2 represent predictors of LVRR.

1044 CHARACTERISTIC AND OUTCOME IN PATIENTS WITH LOW FLOW, LOW GRADIENT AORTIC STENOSIS

Abstract Aim The aim of this study was to assess the prevalence and outcome in patients with severe low flow, low gradient aortic stenosis (LFLG-AS) undergoing transcatheter aortic valve intervention (TAVI). Methods Patients with LFLG AS undergoing TAVI from 2013 to 2022 were prospectively collected. Clinical, imaging data and procedural parameters were collected. LFLG-AS was defined as indexed aortic valve area (iAVA) ≤0.6 cm2/m2, mean transaortic gradient &amp;lt;40 mmHg and stroke volume index &amp;lt;36 ml/m2. Overall population was classified in due subgroups: classical LFLG AS if left ventricular ejection fraction (LVEF) was &amp;lt;50%, and paradoxical in patients with preserved LVEF. The major comorbidities and primary outcome defined as a composite of all-cause mortality and rehospitalization for worsening heart failure (HF) up to 1 year in the different subtypes of severe LFLG AS undergoing TAVI were evaluated. Results The study included 268 patients [81±6 years; 142 (53%) females]; of these, 155 patients (58%) had paradoxical LFLG AS and 113 patients (42%) had LFLG AS with low LVEF. Regarding echocardiography parameters, in the overall population the mean transaortic gradient was 31±6 mmHg, the mean iAVA 0.38±0.08 cm/m2, and the median LVEF 50% (IQR 38-55). Compared with paradoxical LFLG AS, the patients with classical form were characterized by a lower percentage of women (43% vs. 60% p 0.07), worse renal function (46% vs. 30%, p 0.012), and a significantly higher number of cardiovascular disease as coronary artery disease (52% vs. 29%, p &amp;lt;0.001) and atrial fibrillation (37% vs. 23%, p 0.018), resulting in higher Society of Thoracic Surgeons scores [7,34% (IQR: 4.96 to 13,25) versus 5,36% (IQR: 3,22 to 11); p value 0.037]. Higher percentage of patients of New York Heart Association functional class III or IV (61% vs. 27%; p 0.037) was observed in classical LFLG AS. At one-year follow-up, the composite outcome was reported in 49 patients (18%), 21 patients (13%) had paradoxical LFLG AS and 28 patients (24%) had classical form. Kaplan-Meier survival free from the composite outcome was significantly lower in patients with classical LFLG AS compared to those paradoxical LFLG AS (Log-Rank 0,022, Figure 1). Conclusion LFLG AS is a complex population with significant incidence of adverse event at one years. Patients with classical LFLG AS have higher number of risk factor and cardiovascular disease and lower survival compared paradoxical form. Figure 1

Abstract 12136: Multiple Blood Biomarker Approach for Risk Stratification in Patients With Low-Flow Low-Gradient Aortic Stenosis

Background and Objectives: Previous studies have shown that a multiple blood biomarker strategy prior to aortic valve replacement (AVR) may be useful for risk stratification in patients undergoing surgical AVR (SAVR). The usefulness of this approach in patients with low-flow low-gradient aortic stenosis (LF-LG AS) has not been examined. The objective of this study was to determine the prognostic value of combined measures of multiple blood biomarkers in patients with LF-LG AS treated conservatively or by AVR. Methods: 168 patients were prospectively enrolled in the TOPAS (Truly or Pseudo-severe Aortic Stenosis) study at our institute. Clinical and echocardiographic data were collected for each patient. Eight biomarkers of myocardial stress, inflammation, renal function (brain natriuretic peptide, creatine kinase-mb, interleukin-6, alanine transaminase, lactate dehydrogenase, alkaline phosphatase, procalcitonin, ferritin) were measured from blood samples collected at baseline. The cohort was divided into 3 groups according to the number of elevated biomarkers. Uni- and multivariable survival analyses were performed to evaluate the association between the number of elevated biomarkers and all-cause mortality. Results: Mean age was 73 years (68% male). After a median follow-up of 3.41 years, 69 (35%) patients died. Patients with 0-3, 4-6, and &gt;6 elevated biomarkers had 8 years survival estimates of 75%, 52%, and 19%, respectively (log-rank p&lt;0.0001). Using multivariable Cox analysis adjusted for age, sex, BMI, AVR as a time-dependent variable, renal function and STS score, patients with &gt;6 elevated biomarkers had an increased risk of all-cause mortality as compared to the group of patients with 0-3 elevated biomarkers (referent group), HR=3.82, p&lt;.0001, and as compared to the group of patients with 4-6 elevated biomarkers HR=2.81, p&lt;.0001. There was no significant difference in all-cause mortality between patients with 4-6 elevated biomarkers and the referent group p=0.38. Conclusion: In this series of patients with LF-LG AS, a higher number of elevated biomarkers was associated with an increased rate of mortality. These results suggest that a multiple blood biomarkers approach may be useful to enhance the risk stratification in this cohort.

Abstract 15165: Dobutamine Stress Echocardiography in Patients With Low Flow, Low Gradient Aortic Stenosis and Preserved Lvef

Introduction: Guidelines recommend the use of Dobutamine stress echocardiography (DSE) in case of low flow low gradient aortic stenosis (LFLG AS) when left ventricular ejection fraction (LVEF) &lt;50%, but few data support this threshold as most studies have tested DSE when LVEF &lt;35%. Hypothesis: To examine the feasibility of DSE in patients with LFLG AS, and the possible interaction between LVEF and accuracy of projected aortic valve area (AVA proj ) in correctly classifying severe AS defined by Cardiac Computer Tomography (C-CT). Methods: Patients with LFLG AS (aortic mean gradient &lt;40 mmHg &amp; AVA &lt;1.0 cm 2 &amp; stroke volume index (SV i ) &lt;35ml/m 2 ) undergoing DSE were identified from two prospective cohorts, and stratified according to LVEF (&lt;35%, 35-50% and &gt;50%). Severe AS was defined as AVC score ≥2000 AU in males, and ≥1200 AU in females on C-CT. Results: Of 214 patients, 65 (30%) presented with LVEF &lt;35%, 58 (27%) with LVEF 35-50%, and 91 (43%) with LVEF &gt;50%. 97 patients presented with severe AS (32 vs 21 vs 44, p=0.26). An inverse relationship was seen between LVEF and left ventricular diameter (60±10mm vs 54±7mm vs 47±6mm, p&lt;0.01). Although resting SV i was different between groups (26.4±6.4mL vs 27.3±5.6 vs 29.6±5.7, p&lt;0.01), no significant differences in SV i change was seen during DSE (7.3±5.9mL vs 5.5±6.2mL vs 6.7±6.7mL, p=0.30), and patients with LVEF &lt;35% were more likely to demonstrate flow-reserve, defined as an increase in SVi &gt;20%; 39 (63%) vs 21 (36%) vs 44 (49%), p=0.01. AVA proj provided similar AUCs (p=0.31) (Figure 1) and cut-off points in classifying severe AS across LVEF groups: LVEF&lt;35%: 1.02 cm 2 /accuracy 74%, vs LVEF 35-50%: 0.82cm 2 /accuracy 72% vs LVEF &gt;50%: 0.9cm 2 /accuracy 65%. Conclusion: DSE leads to similar increases in stroke volume index (SV i ) in patients with LVEF &gt;50% compared with LVEF ≤50%. Furthermore, the projected aortic valve area (AVA proj ) provides good accuracy for identification of true-severe AS, regardless of LVEF stratum.

Mitral regurgitation and in-hospital mortality in patients with heart failure and low flow low gradient aortic stenosis

Abstract Funding Acknowledgements Type of funding sources: None. Aim this study sought to determine the prevalence, clinical impact, and in-hospital outcome of moderate to severe mitral regurgitation (MR) in patients with low-flow, low-gradient aortic stenosis (LFLG-AS) hospitalized for heart failure (HF). Methods Patients with aortic valve thickness and aortic velocities &amp;gt;2.5 m/s hospitalized for heart failure in a single referral center were prospectively enrolled from 2013 to 2021. LFLG-AS was defined as indexed aortic valve area (iAVA) ≤0.6 cm2/m2, mean transaortic gradient &amp;lt;40 mmHg and stroke volume index &amp;lt;36 ml/m2. Complete demographic, clinical characteristics and echocardiographic data were collected. Mitral regurgitation severity was graded according to current guidelines. Patients were divided into two subgroups according to MR severity: no/mild MR vs moderate/severe MR. In hospital all cause death has been considered as the primary outcome. Results A total of 136 patients (78 ± 9 yy; 68 (50%) male) hospitalized for HF with a new diagnosis of LFLG-AS were included in the study. The most frequent comorbidities were hypertension (121, 89%), dyslipidemia (106, 78%), chronic kidney disease (85, 63%), diabetes (56, 41%) and obesity (44, 32%). Atrial fibrillation/flutter was detected in 61 (45%) patients. Moderate to severe MR was detected in 33%. Mean functional NYHA class was 2,8 ± 0,8. Concerning echocardiographic evaluation, the mean gradient of the aortic valve was 26 ± 7 mmHg and the mean iAVA was 0.42 ± 0.10 cm2/m2. The mean left ventricular ejection fraction (LV EF) was 46 ± 13%. Paradoxical LFLG-AS with a preserved LV EF was detected in 73 patients (54%) and the LFLG-AS with a low LV EF was detected in 63 (46%). In this population, 26 patients (19%) underwent surgical valvular replacement, 15 patients (11%) had aortic percutaneous valvuloplasty and 33 patients (24%) underwent TAVI. The remaining patients (45%, n = 62) were maintained under optimized medical therapy. In-hospital death occurred in 17 (12,5%) patients (just 1 for non-cardiovascular causes). Moderate/severe MR was detected in 44 (33%) patients. When comparing the two subgroups statistically significant differences between age (p = 0,035), male sex (p = 0,028), atrial fibrillation/flutter (p = 0,003), obesity (p = 0,040) and in-hospital mortality (p = 0,013) were detected. In the overall population the multivariate regression analysis showed that only the presence of moderate /severe MR was a significant independent predictor of all-cause in-hospital death (p = 0.017 ; OR 3.571 ; IC 1.257-10.151). Conclusion. Moderate to severe MR is frequently detected in patients with LFLG AS and HF. In this peculiar cohort significant MR has a negative impact on outcome and is independently associated with in-hospital mortality.

Risk prediction in patients with low-flow, low-gradient aortic stenosis and reduced ejection fraction undergoing TAVI

ObjectivePatients with low-flow, low-gradient aortic stenosis (LFLG AS) and reduced left ventricular ejection fraction (LVEF) are known to suffer from poor prognosis after transcatheter aortic valve implantation (TAVI). This study...

535 Right ventricular dysfunction is independent predictor of in-hospital mortality in patients with low flow low gradient aortic stenosis

Abstract Aims Aim of the study is to assess the prevalence and in-hospital death in patients with low flow low gradient aortic stenosis (LFLG-AS) and right ventricular dysfunction (RVD) hospitalized for heart failure in a single referral centre. Methods and results Complete demographic, clinical characteristics, and imaging data were collected. Patients with LFLG AS hospitalized for heart failure were prospectively enrolled from 2013 to 2021. LFLG-AS was defined as indexed aortic valve area (iAVA) ≤0.6 cm2/m2, mean transaortic gradient &amp;lt; 40 mmHg, and stroke volume index &amp;lt;36 ml/m2. RVD was defined as tricuspid annular plane systolic excursion (TAPSE) &amp;lt; 16 mm at baseline in apical four chamber view according to current guidelines. Patients were divided into two subgroups according to the presence or absence of RVD. In hospitals all cause death has been considered as the primary outcome. A total of 130 patients [78 ± 10 yy; 67 (51%) male] with new diagnosis of LF-LG AS were included in the study. The most frequent comorbidities were hypertension (88.5%; n = 114), dyslipidaemia (74%; n = 96), and diabetes (38%; n = 49). Concomitant coronary artery disease and history of stroke were reported in 19% (n = 24) and 9% (n = 11), respectively. Society of thoracic surgeons score in overall population was 12.6 ± 4.5. Regarding echocardiographic evaluation, the mean transaortic gradient was 25.81 ± 7.42 mmHg and the mean iAVA was 0.42 ± 0.10 cm/m2. The mean left ventricular ejection fraction (LV EF) was 46 ± 13%. LFLG AS with a preserved LV EF was detected in 69 patients (53%) and the LFLG AS with a low LV EF was detected in 61 patients (47%). 26 patients (20%) underwent surgical valve replacement, 14 patients (11%) had aortic percutaneous valvuloplasty and 31 patients (24%) underwent TAVI. The remaining patients (45%, n = 59) were maintained under optimized medical therapy. In-hospital death occurred in 16 patients. When compared patients with RVD with those without a higher prevalence of atrial fibrillation/flutter (n = 21, 36%; P = 0.042) and in hospital death was observed (n = 8; 28%; n = 8, 8%; P = 0.026). In the overall population at multivariate regression analysis only RVD was a significant independent predictor of all-cause in-hospital death (P = 0.028; OR: 3.44; CI: 1.146–10.334). Conclusions RVD can be detected in more than one quarter of patient with new diagnosis of LFLG AS and is an independent predictor of all-cause in-hospital death. Quantification of right ventricular systolic function in these complex population give important information in identifying patients and higher risk requiring more aggressive therapy.

454 Mitral regurgitation and in-hospital mortality in patients with heart failure and low flow low gradient aortic stenosis

Abstract Aims This study sought to determine the prevalence, clinical impact, and in-hospital outcome of moderate to severe mitral regurgitation (MR) in patients with low-flow, low-gradient aortic stenosis (LFLG-AS) hospitalized for heart failure (HF). Methods and results Patients with aortic valve thickness and aortic velocities &amp;gt;2.5 m/s hospitalized for heart failure in a single referral centre were prospectively enrolled from 2013 to 2021. LFLG-AS was defined as indexed aortic valve area (iAVA) ≤0.6 cm2/m2, mean transaortic gradient &amp;lt;40 mmHg, and stroke volume index &amp;lt;36 ml/m2. Complete demographic, clinical characteristics, and echocardiographic data were collected. Mitral regurgitation severity was graded according to current guidelines. Patients were divided into two subgroups according to MR severity: no/mild MR vs. moderate/severe MR. In hospital all cause death has been considered as the primary outcome. A total of 136 patients [78 ± 9 yy; 68 (50%) male] hospitalized for HF with a new diagnosis of LFLG-AS were included in the study. The most frequent comorbidities were hypertension (121, 89%), dyslipidemia (106, 78%), chronic kidney disease (85, 63%), diabetes (56, 41%), and obesity (44, 32%). Atrial fibrillation/flutter was detected in 61 (45%) patients. Moderate to severe MR was detected in 33%. Mean functional NYHA class was 2.8 ± 0.8. Concerning echocardiographic evaluation, the mean gradient of the aortic valve was 26 ± 7 mmHg and the mean iAVA was 0.42 ± 0.10 cm2/m2. The mean left ventricular ejection fraction (LV EF) was 46 ± 13%. Paradoxical LFLG-AS with a preserved LV EF was detected in 73 patients (54%) and the LFLG-AS with a low LV EF was detected in 63 (46%). In this population, 26 patients (19%) underwent surgical valvular replacement, 15 patients (11%) had aortic percutaneous valvuloplasty, and 33 patients (24%) underwent TAVI. The remaining patients (45%, n = 62) were maintained under optimized medical therapy. In-hospital death occurred in 17 (12.5%) patients (just 1 for non-cardiovascular causes). Moderate/severe MR was detected in 44 (33%) patients. When comparing the two subgroups statistically significant differences between age (P = 0.035), male sex (P = 0.028), atrial fibrillation/flutter (P = 0.003), obesity (P = 0.040), and in-hospital mortality (P = 0.013) were detected. In the overall population the multivariate regression analysis showed that only the presence of moderate/severe MR was a significant independent predictor of all-cause in-hospital death (P = 0.017; OR: 3.571; CI: 1.257–10.151). Conclusions Moderate to severe MR is frequently detected in patients with LFLG AS and HF. In this peculiar cohort significant MR has a negative impact on outcome and is independently associated with in-hospital mortality.

Risk prediction in patients with classical Low-flow, low-gradient aortic stenosis undergoing TAVI

Abstract Background Patients with classical low-flow, low-gradient aortic stenosis (LFLG AS) undergoing transcatheter aortic valve implantation (TAVI) are known to suffer from poor prognosis. Risk prediction is difficult and predictors of outcome are scarce in this complex patient subset. Purpose This study aimed to develop a simple score system for risk prediction in patients with classical LFLG AS scheduled for TAVI including baseline clinical, echocardiographic and computed tomography (CT) parameters. Methods Among 9,150 patients undergoing TAVI (2008–2019) at five German centers, patients with classical LFLG AS were screened for availability of sufficient CT data for aortic valve calcification (AVC) quantification. Score variables were defined as all variables included into the best performing multivariable regression model. Score performance was assessed by Kaplan-Meier analysis for the endpoint of 1-year all-cause as well as c-index calculation. Results A total of 718 patients were included into the study. Predictors of all-cause mortality were male sex (HR 1.27 [0.98, 1.65], p=0.068), chronic obstructive pulmonary disease (HR 1.59 [1.21,2.08], p&amp;lt;0.001), atrial fibrillation (HR 1.33 [1.03,1.70], p=0.026), stroke volume index (HR 0.96 [0.94, 0.98], p&amp;lt;0.001), non-transfemoral access (HR 1.44 [1.09,1.91], p=0.011), pulmonary hypertension (HR 1.58 [1.20,2.08], p=0.0012) and low AVC density (HR 1.49 [1.16,1.90], p=0.0016). A score system was developed ranging from 0 points to 11 points. Kaplan-Meier analysis for low (0–2 points), moderate (3–6 points) and high score (&amp;gt;6 points) demonstrated 1-year mortality rates of 20.9%, 28.9% and 64.3% (p&amp;lt;0.001), respectively. C-index for prediction of 1-year mortality was 0.69 (95%-CI 0.65–0.84). The RELiEF TAVI score outperformed classical risk prediction models like the logistic euroSCORE (c-index 0.60 [95%-CI 0.51–0.72], p=0.013), the EuroSCORE II (c-index 0.57 [95%-CI 0.45–0.70], p=0.039) and the STS PROM (c-index 0.60 [0.48–0.70], p=0.035). Conclusions The RELiEF TAVI score is based on simple clinical, echocardiographic and CT parameters and might serve as a helpful tool for risk prediction in the vulnerable subset of patients with classical LFLG AS scheduled for TAVI. Funding Acknowledgement Type of funding sources: None. RELiEF TAVI Score

107 Low-flow low-gradient aortic stenosis: aortic valve area estimated by continuity equation versus simplified method of projected aortic valve area

Abstract Introduction The evaluation of real severity of "low-flow low-gradient" aortic stenosis (LFLG AS) is particularly challenging. TOPAS study demonstrated that projected aortic valve area at a normal transvalvular flow rate (AVAproj) derived from dobutamine stress echocardiography (DSE) is superior to the traditional Doppler indices to discriminate true severe-AS and pseudosevere-AS. Purpose To compare two echocardiographic methods to estimate severity of LFLG AS with DSE (aortic valve area (AVA) estimated by continuity equation (AVA-CE) and simplified method of AVAproj) in patients (pts) with low transvalvular flow rate (&amp;lt;250mL/seg). Methods Unicentric, retrospective study, that included pts with LFLG AS undergoing DSE with low dose dobutamine protocol, during Nov 2013-Dec 2018 period. Evaluation at rest and peak DSE of vital signs, mean transaortic gradient, aortic VTI, LVOT VTI and VTI ratio, valvulo-arterial impedance (ZVA), AVA-CE, simplified method of AVAproj and global longitudinal strain (GLS). Results A total of 27 DSE were performed in 23 different pts, mean age of 76 ± 8 years, 82% male. At rest 55% in sinus rhythm, mean heart rate (HR) was 76 ± 12 bpm, mean systolic arterial pressure (SAP) was 122 ± 22 mmHg, mean ZVA 4.3 ± 2 mmHg/ml/m2; mean diameter of LVOT was 21,7 ± 2,6cm, mean of mean aortic gradients 21 ± 7 mmHg, 67% of pts had a VTI ratio at rest compatible with severe AS and remaining compatible with moderate AS. Estimated mean AVA-CE was 0.86 ± 0.29 cm2 with 67% of pts classified as severe AS. Mean left ventricular ejection fraction at rest was 31 ± 9%, systolic volume index 28,7 ± 8 mL/m2 and GLS -5,9%. During low dose perfusion protocol of dobutamine 100% patients remained asymptomatic, mean HR was 110 ± 25 bpm, mean SAP was 123 ± 26 mmHg, mean ZVA 3.6 ± 1.7 mmHg/mL/m2, mean of mean aortic gradients 28 ± 9mmHg, 37% of pts presented VTI ratio compatible with severe AS and remaining compatible with moderate AS. Mean flow reserve was 16 ± 16% and mean GLS-7.2%. AVA-CE was 1,06 ± 0,35 cm2 with 56% of pts classified as severe AS and mean projected AVA was 1.01 ± 0.22cm2, without significant difference in AVA estimated by the two methods (p = 0.344). Projected AVA allowed re-classification of AS in 22% of pts (5 patients), with 31% of severe AS reclassified as moderate AS while AVA-CE allowed re-classification in 13% (3 patients), with 19% of severe AS reclassified as moderate AS. Considering medium follow up of 24 months, 6 patients were submitted aortic valve replacement surgery and another 6 patients to transcatheter aortic valve replacement. The simplified projected valve area calculation show no significant therapeutic impact in the selection of this patients. Conclusion The simplified projected valve area calculation is technically feasible and accessible. This study shows a good correlation in pts with low cardiac flow. If AVAproj method had been used 2 extra patients would have been reclassified during DSE.

Low Gradient Aortic Stenosis: Role of Echocardiography

The purpose of this paper is to review the current role of echocardiography in the evaluation of patients with low gradient severe aortic stenosis (LG severe AS). Discordant grading of AS severity, in which a small aortic valve area coexists with a small gradient, can result in diagnostic and therapeutic dilemmas. Transthoracic, transesophageal, and stress echocardiography play pivotal roles in reconciling the discordance and clarifying AS severity. Three physiologic categories of LG severe AS can be identified (classical low flow (LF) LG AS, paradoxical LF-LG AS, and normal flow LG AS), each with different prognostic and therapeutic implications. Echocardiographic measures of the severity of the valve stenosis, left ventricular function (and functional reserve), and right heart disease provide important prognostic information to assist with patient management. A systematic comprehensive approach using echocardiography is essential in LG severe AS to understand the reason for the discordant hemodynamics, to confirm AS severity, and to guide therapeutic decision-making.

Invasive Assessment of Low Flow Low Gradient Aortic Stenosis

Background: Low flow low gradient Aortic stenosis (LF-LG AS) is seen in about 5-10% of patients with severe AS and it is characterised by a discordance between the aortic valve area (AVA) <1 cm2 and/or index (i) AVA <0.6 cm2/m2(consistent with severe AS) and the mean gradient (MG)<40 mmHg, (consistent with non-severe AS). Non-invasive assessment of LF-LG AS can be challenging. Aim: We hypothesised that invasive assessment of LF-LG AS in the cardiac catheterisation laboratory with dobutamine stress testing can accurately assess AS severity and guide management. Methods: We conducted a single centre, single operator dependent retrospective study on 18 patients identified to have LF-LG AS by echocardiography. Invasive assessment involved measurement of simultaneous gradients across the aortic valve with measurement of cardiac output (CO) using thermodilution. Clinical outcome following surgical or transcatheter aortic valve replacement (SAVR or TAVR) or medical management for patients with true and pseudo AS was studied. Results: 11 patients had true severe AS, 5 patients had pseudo AS and 2 had inconclusive finding (See table).Tabled 1True ASPseudo ASInconclusiveP valueBaseline MG26.91 ± 4.1124.08 ± 4.7715.75 ± 1.770.054Post MG39.64 ± 5.4129.88 ± 10.1922.5 ± 0.710.006Baseline iAVA0.39 ± 0.090.52 ± 0.050.31 ± 0.100.022Post iAVA0.43 ± 0.10.68 ± 0.10.33 ± 0.060.0003Baseline CO3.66 ± 1.034.2 ± 0.783.48 ± 0.220.513Post CO5.07 ± 1.345.34 ± 0.954.75 ± 1.910.852Max.Dobutamine dose(mcg/kg/min)22.27 ± 13.326 ± 13.4230 ± 14.140.7126 out of 11 true severe AS patients underwent SAVR or TAVR and all survived beyond 3 years. Of the 5 patients treated conservatively, mortality was 40% in 1 year and 100% in 3 years. 1 patient with pseudo AS underwent SAVR while 4 were medically managed. All patients with pseudo AS survived beyond 1 year. Open table in a new tab 6 out of 11 true severe AS patients underwent SAVR or TAVR and all survived beyond 3 years. Of the 5 patients treated conservatively, mortality was 40% in 1 year and 100% in 3 years. 1 patient with pseudo AS underwent SAVR while 4 were medically managed. All patients with pseudo AS survived beyond 1 year. Conclusion: Invasive assessment of LF-LG AS is an alternative to accurately assess the true severity of AS and guide appropriate management to improve long term outcomes.

FLOW RATE NOT STROKE VOLUME IS A SUPERIOR PROGNOSTIC MARKER OF TRANSORTIC FLOW AND FLOW RESERVE IN PATIENTS WITH LOW-FLOW LOW-GRADIENT AORTIC STENOSIS UNDERGOING LOW-DOSE DOBUTAMINE ECHOCARDIOGRAPHY

The objectives of low-dose dobutamine stress echocardiography (LDDSE) in low-flow low-gradient aortic stenosis (LFLG AS) are both to normalise transvalvular flow, at which juncture the aortic valve area informs the true AS severity, and to assess flow reserve. Conventionally, these assessments are

Dobutamine Stress Echocardiography for Management of Low-Flow, Low-Gradient Aortic Stenosis

BackgroundIn the American College of Cardiology/American Heart Association guidelines, patients are considered to have true-severe stenosis when the mean gradient (MG) is ≥40 mm Hg with an aortic valve area (AVA) ≤1 cm2 during dobutamine stress echocardiography (DSE). However, these criteria have not been previously validated. ObjectivesThe aim of this study was to assess the value of these criteria to predict the presence of true-severe AS and the occurrence of death in patients with low-flow, low-gradient aortic stenosis (LF-LG AS). MethodsOne hundred eighty-six patients with low left ventricular ejection fraction (LVEF) LF-LG AS were prospectively recruited and underwent DSE, with measurement of the MG, AVA, and the projected AVA (AVAProj), which is an estimate of the AVA at a standardized normal flow rate. Severity of AS was independently corroborated by macroscopic evaluation of the valve at the time of valve replacement in 54 patients, by measurement of the aortic valve calcium by computed tomography in 25 patients, and by both methods in 8 patients. According to these assessments, 50 of 87 (57%) patients in the study cohort had true-severe stenosis. ResultsPeak stress MG ≥40 mm Hg, peak stress AVA ≤1 cm2, and the combination of peak stress MG ≥40 mm Hg and peak stress AVA ≤1 cm2 correctly classified AS severity in 48%, 60%, and 47% of patients, respectively, whereas AVAProj ≤1 cm2 was better than all the previous markers (p < 0.007), with 70% correct classification. Among the subset of 88 patients managed conservatively (47% of the cohort), 52 died during a follow-up of 2.8 ± 2.5 years. After adjustment for age, sex, functional capacity, chronic kidney failure, and peak stress LVEF, peak stress MG and AVA were not predictors of mortality in this subset. In contrast, AVAProj ≤1 cm2 was a strong predictor of mortality under medical management (hazard ratio: 3.65; p = 0.0003). ConclusionsIn patients with low LVEF LF-LG AS, the DSE criteria of a peak stress MG ≥40 mm Hg, or the composite of a peak stress MG ≥40 mm Hg and a peak stress AVA ≤1 cm2 proposed in the guidelines to identify true-severe AS and recommend valve replacement, have limited value to predict actual stenosis severity and outcomes. In contrast, AVAProj better distinguishes true-severe AS from pseudo-severe AS and is strongly associated with mortality in patients under conservative management. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS]; NCT01835028)

An Alternative Method to Calculate Simplified Projected Aortic Valve Area at Normal Flow Rate.

BackgroundSimplified projected aortic valve area (EOAproj) is a valuable echocardiographic parameter in the evaluation of low flow low gradient aortic stenosis (LFLG AS). Its widespread use in clinical practice is hampered by the laborious process of flow rate (Q) calculation.ObjetiveThis study proposes a less burdensome, alternative method of Q calculation to be incorporated in the original formula of EOAproj and measures the agreement between the new proposed method of EOAproj calculation and the original one.MethodsRetrospective observational single-institution study that included all consecutive patients with classic LFLG AS that showed a Q variation with dobutamine infusion ≥ |15|% by both calculation methods.ResultsTwenty-two consecutive patients with classical LFLG AS who underwent dobutamine stress echocardiography were included. Nine patients showed a Q variation with dobutamine infusion calculated by both classical and alternative methods ≥ |15|% and were selected for further statistical analysis. Using the Bland-Altman method to assess agreement we found a systematic bias of 0,037 cm2 (95% CI 0,004 - 0,066), meaning that on average the new method overestimates the EOAproj in 0,037 cm2 compared to the original method. The 95% limits of agreement are narrow (from -0,04 cm2 to 0,12 cm2), meaning that for 95% of individuals, EOAproj calculated by the new method would be between 0,04 cm2 less to 0,12 cm2 more than the EOAproj calculated by the original equation.ConclusionThe bias and 95% limits of agreement of the new method are narrow and not clinically relevant, supporting the potential interchangeability of the two methods of EOAproj calculation. As the new method requires less additional measurements, it would be easier to implement in clinical practice, promoting an increase in the use of EOAproj.

B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin for Risk Stratification in Low-Flow, Low-Gradient Aortic Stenosis: A Substudy of the TOPAS Study

ObjectivesThe objective of this study was to determine the prognostic value of combined measures of B-type natriuretic peptide (BNP) and high-sensitivity cardiac troponin T (hsTnT) in patients with low-flow, low-gradient aortic stenosis (LF-LG AS) who had either a preserved or reduced left ventricular ejection fraction (LVEF). BackgroundAn elevated BNP level is associated with increased risk of mortality in patients with LF-LG AS. The incremental prognostic value of hsTnT in these patients is unknown. MethodsNinety-eight patients (74 ± 10 years; 75% men) with LF-LG AS (LVEF <50% and/or stroke volume index <35 ml/m2, mean gradient <40 mm Hg, indexed aortic valve area <0.6 cm2/m2) who were prospectively enrolled in the TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study were included. The cohort was divided into 3 groups according to BNP and hsTnT levels: group A: BNP <550 pg/ml and hsTnT <15 ng/l; group B: BNP ≥550 pg/ml or hsTnT ≥15 ng/l; and group C: BNP ≥550 pg/ml and hsTnT ≥15 ng/l. The primary endpoint was all-cause mortality. ResultsTwenty-seven patients (27%) were in group A, 39 (40%) were in group B, and 32 (33%) were in group C. During a median follow-up of 2.8 years, 43 patients died. Two-year mortality was higher in group C (41 ± 9%) than in group B (23 ± 7%) and group A (5 ± 4%) (p = 0.002). In group B, there was no significant difference in 2-year mortality rates between the subgroup with hsTnT ≥15 ng/l (n = 29) and the subgroup with BNP ≥550 pg/ml (n = 10) (26 ± 9% vs. 11 ± 10%, respectively; p = 0.21). In multivariable analysis adjusted for age, type of treatment (aortic valve replacement vs. conservative therapy), coronary artery disease, and LVEF, being in group C remained independently associated with an increased risk of mortality (hazard ratio [HR]: 4.25; p = 0.023), and group B tended to have higher mortality (HR: 3.63; p = 0.058) compared with group A. ConclusionsThis study demonstrated the usefulness of combined measures of BNP and hsTnT to enhance risk stratification in patients with LF-LG AS. Patients with elevation of both BNP and hsTnT had a markedly increased risk of mortality. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS]; NCT01835028)